Method for retaining a vascular stent on a catheter

ABSTRACT

A method of securely mounting a stent on a balloon of a catheter. The method generally includes crimping a stent on a balloon of a catheter at least one time, and positioning the balloon with the stent thereon within a polished bore of a mold formed at least in part of a metallic material. The balloon is pressurized and heated within the mold, or within a sheath, in two stages as the stent is restrained from radially expanding. The method may include crimping the stent onto the balloon one or two times during processing. The method increases retention of the stent on the balloon catheter following sterilization.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application claims priority to and is a division of U.S. Ser. No.13/091,847 filed Apr. 21, 2011, which is a division of U.S. Ser. No.11/521,993 filed Sep. 15, 2006, now U.S. Pat. No. 7,947,207, which is acontinuation-in-part of U.S. Ser. No. 11/453,747 filed Jun. 15, 2006,now U.S. Pat. No. 7,763,198, which is a continuation-in-part of U.S.Ser. No. 11/105,085 filed Apr. 12, 2005, now U.S. Pat. No. 7,563,400,the entirety of which are incorporated herein by reference.

BACKGROUND OF THE INVENTION

This invention relates generally to catheters and stents, andparticularly to methods for retention of stents on intravascular stentdelivery catheters.

In percutaneous transluminal coronary angioplasty (PTCA) procedures aguiding catheter is advanced in the patient's vasculature until thedistal tip of the guiding catheter is seated in the ostium of a desiredcoronary artery. A guidewire is first advanced out of the distal end ofthe guiding catheter into the patient's coronary artery until the distalend of the guidewire crosses a lesion to be dilated. A dilatationcatheter, having an inflatable balloon on the distal portion thereof, isadvanced into the patient's coronary anatomy over the previouslyintroduced guidewire until the balloon of the dilatation catheter isproperly positioned across the lesion. Once properly positioned, thedilatation balloon is inflated with inflation fluid one or more times toa predetermined size at relatively high pressures so that the stenosisis compressed against the arterial wall and the wall expanded to open upthe vascular passageway. Generally, the inflated diameter of the balloonis approximately the same diameter as the native diameter of the bodylumen being dilated so as to complete the dilatation but not overexpandthe artery wall. After the balloon is finally deflated, blood flowresumes through the dilated artery and the dilatation catheter and theguidewire can be removed therefrom.

In such angioplasty procedures, there may be restenosis of the artery,i.e. reformation of the arterial blockage, which necessitates eitheranother angioplasty procedure, or some other method of repairing orstrengthening the dilated area. To reduce the restenosis rate ofangioplasty alone and to strengthen the dilated area, physicians nownormally implant an intravascular prosthesis, generally called a stent,inside the artery at the site of the lesion. Stents may also be used torepair vessels having an intimal flap or dissection or to generallystrengthen a weakened section of a vessel or to maintain its patency.Stents are usually delivered to a desired location within a coronaryartery in a contracted condition on a balloon of a catheter which issimilar in many respects to a balloon angioplasty catheter, and expandedwithin the patient's artery to a larger diameter by expansion of theballoon. The balloon is deflated to remove the catheter and the stentleft in place within the artery at the site of the dilated lesion. Seefor example, U.S. Pat. No. 5,507,768 (Lau et al.) and U.S. Pat. No.5,458,615 (Klemm et al.), which are incorporated herein by reference.

The stent must be securely yet releasably mounted on the catheterballoon for delivery and deployment at the desired location in apatient's body lumen. If the stent becomes dislodged from or movedrelative to the balloon during delivery, the system will not correctlyimplant the stent in the body lumen. However, the stent can't be sostrongly fixed to the balloon that it inhibits expansion of the balloonand/or release of the stent once the balloon is positioned at thedesired location. One difficulty has been retention of stents, includingstents having a drug delivery layer. The mounting process used to securethe drug delivery stent to the balloon must not damage the stent.Furthermore, the stent retention process must not damage a stentincluding a drug or the matrix material containing the drug. It would bea significant advance to provide a catheter balloon having improvedretention of a stent, for example, a drug delivery stent, and withoutinhibiting balloon or stent function. The present invention satisfiesthese and other needs.

SUMMARY OF THE INVENTION

One aspect of the present invention is a method of mounting a stent on aballoon catheter, including positioning the stent on a balloon of theballoon catheter, and applying a radially compressive force on an outersurface of the stent, thereby decreasing the outer diameter of the stenton the balloon catheter. The balloon is then pressurized and heatedwhile restricting radial expansion of the outer surface of the stentduring a first period of time. Thereafter, the balloon is thenpressurized and heated while restricting radial expansion of the outersurface of the stent during a second period of time. In one aspect ofthe invention, the second time period may have a duration of about 15seconds to about 48 hours. The balloon may be pressurized to a pressureof about 5 pounds per square inch (3.5 newtons per square centimeter) toabout 300 pound per square inch (207 newtons per square centimeter)during at least one of the first time period and the second time period.

In one aspect, the pressurizing and heating of the balloon may beperformed in a mold configured to restrict the radial expansion of theouter surface of the stent. In another aspect, the pressurizing andheating of the balloon may be performed in a sheath configured torestrict the radial expansion of the outer surface of the stent. Stillanother aspect of the present invention is restricting radial expansionof the outer surface of the stent to about a final stent outer diameter.Another aspect of the present invention is applying a transientplasticizing agent to the balloon prior to heating and pressurizing theballoon.

The heating of the balloon may be performed by applying heat usingconvection through the mold. The heating of the balloon may be performedby heating the mold by contacting a surface of the mold with aconductive heating element member which heats the mold purely byconduction and which provides temperature control to the mold with atolerance of about ±1 degree to about ±2 degrees F. In one aspect, theheating of the balloon is performed by applying heat using forced airconvection. In another aspect of the invention, the heating of theballoon is performed by applying heat using an oven. In still anotheraspect of the present invention, the balloon is heated to a temperatureapproximately equal to the glass transition temperature of the balloonduring at least one of the first time period and the second time period.

In still another aspect of the invention the stent is a drug deliverystent and mounting the stent on the balloon and increasing stentretention is performed without damaging the drug delivery layer of thestent.

Yet another aspect of the present invention includes cooling the stentafter applying heat and pressure to the balloon. The cooling may appliedduring a third period of time. The cooling may be controlled. In oneaspect of the present invention, the balloon remains pressurized duringthe cooling.

Yet another aspect of the present invention is a method of mounting astent on a balloon catheter, including positioning a stent on a ballooncatheter, the balloon catheter having an elongated shaft with aninflation lumen and a guidewire lumen and an inflatable balloon on adistal shaft section with an interior in fluid communication with theinflation lumen, and the stent having an open-walled body of stentstruts with gaps between adjacent stent struts. At least one radiallycompressive force is applied on an outer surface of the stent, therebydecreasing the outer diameter of the stent on the balloon catheter.Thereafter, the balloon is heated and inflation media is introduced intothe interior of the balloon for a first period of time to radiallyexpand the balloon with the stent restrained from radially expanding,wherein the balloon expands into the stent gaps to embed the stent in anouter surface of the balloon. The inflation media may then be removedfrom the balloon interior. Thereafter, the balloon is heated andinflation media is introduced into the interior of the balloon for asecond period of time to radially expand the balloon with the stentrestrained from radially expanding. The stent may be restrained fromradially expanding by using a mold, for example a split mold, or asheath. The balloon may further expand into the stent gaps to moresecurely embed the stent in an outer surface of the balloon. This mayincrease stent retention on the balloon catheter after sterilizing thestent, for example, by EtO sterilization.

One other aspect of the present invention is a method of increasingretention of an intravascular device on a balloon catheter, includingcrimping the intravascular device onto a balloon of the ballooncatheter, a first stage of heating and pressurizing the balloon, and asecond stage of heating and pressurizing the balloon. The method mayfurther include crimping the intravascular device onto a balloon of theballoon catheter at least one additional time.

One aspect of the present invention is directed to a method of mountinga stent on a stent delivery balloon catheter. Yet another aspect of theinvention is a method of mounting a drug delivery stent on a balloon,and a stent delivery balloon catheter produced therefrom. Still anotheraspect of the invention is a method that securely mounts a drug deliverystent on a balloon catheter without damaging the drug delivery layer ofthe stent.

In one aspect of the invention, the method generally comprisespositioning a stent, for example, a drug delivery stent, on a balloon ofa balloon catheter, and positioning the balloon with the stent thereonwithin a polished bore of a mold formed at least in part of a metallicmaterial. In yet a further aspect of the invention, the stent is a drugdelivery stent, and the balloon is pressurized and heated within themold to mount the stent on the balloon, without damaging the drugdelivery layer of the stent. The mold radially restrains the stent fromexpanding when the balloon is pressurized therein, so that the ballooncan be forced into the gaps in the stent wall using inflation pressureshigher than those which normally cause radial expansion of the stent.The bore of the mold is defined by a polished inner surface with apolished finish which is sufficiently smooth so that contact andrelative movement between the stent and polished inner surface of themold does not roughen or otherwise damage or create a texture on thedrug delivery layer of the stent. As a result, the release rate of thedrug from the drug delivery layer is substantially equal to the releaserate prior to stent mounting. In another aspect of the invention, thesmooth surface of the drug delivery layer, which is free of roughnessand irregularities caused by the stent mounting, provides the drugdelivery layer with a uniform thickness which is within the normalvariance produced by the method used to form the drug delivery layer.Additionally, the inner surface of the mold does not cause the drugdelivery layer to transfer drug to the inner surface of the mold duringthe stent mounting, so that the amount of drug present in the drugdelivery layer is substantially equal to the amount prior to stentmounting.

In yet another aspect of the invention, the drug delivery layer of thestent is a coating applied to a surface of the radially expandabletubular body of the stent. However, a variety of suitable configurationsmay be used as are well known in the art, including embodiments in whichthe tubular body of the stent is itself formed of a drug deliverymatrix, or the drug delivery layer is a tubular sleeve on a surface ofthe body of the stent. Additionally, the drug delivery layer should beunderstood to broadly refer to configurations which deliver or presentone or more drugs by any of a variety of suitable mechanisms includingeluting the drug from the layer, bioabsorption of a drug deliverymatrix, and the like. The stent may be biostable and/or bioabsorable.The terminology “drug” as used herein should be understood to refer to avariety of therapeutic and diagnostic agents. In a further aspect of theinvention, the drug is intended to prevent or inhibit restenosis.

The balloon is heated by heating the mold using a heat transfer mediumwhich provides temperature control to the mold with a tolerance of about±1 degree to about ±2 degrees Fahrenheit (F)). In still another aspectof the invention, heating the mold comprises submerging the mold in aliquid bath, or contacting the surface of the mold with a conductiveheating element. As a result, the heat transfer medium heats the moldprimarily by conduction, and provides for finer temperature control andquicker heating than is provided by heating methods which heat primarilyby convection (e.g., heating with hot air). In contrast, heating withhot air provides a heating tolerance of about ±10 degrees. In apresently preferred embodiment, the heat transfer medium is a conductiveheating element such as a platen (e.g., a heated flat metal plate)configured to provide uniform heating of the balloon within the moldwhen the platen is in contact with the mold. Thus, the temperature isuniform (i.e., within about ±2 degrees F.) along the length of thesection of the mold exposed to the heating medium, and the temperatureat any given point of the heated length remains constant (i.e., within±2 degrees F.) during the heating. With the metal platen pressed againstan outer surface of the mold, the platen heats purely by conduction(unlike a hot circulating heating medium which heats by both conductionand convention), and provides for finer temperature control at thesurface of the mold than a hot liquid bath or hot air. The temperaturecontrol provided by the heat transfer medium prevents the drug frombeing exposed to an elevated temperature which is above the thermallimit of the drug, while allowing the balloon to be quickly heated to asufficiently high temperature to soften the balloon material duringstent mounting.

In still another aspect of the invention, in which the heat transfermedium is a hot liquid bath, the mold is configured to seal the bore ofthe mold with the catheter therein, so that the mold is submergedwithout liquid or humidity from the liquid bath contacting the drugdelivery stent in the mold. As a result, the drug delivery layer is notdissolved or otherwise damaged by exposure when the mold is submerged inthe liquid bath.

The metallic material of the mold allows the mold to be machined withtight dimensional tolerances, to provide an accurate and uniform borediameter. Additionally, the metallic material of the mold providessufficient strength, even at elevated temperature, so that the moldradially restrains the stent during the stent mounting procedure withoutthe diameter of the mold bore increasing. Thus, unlike a radialrestraining member which expands somewhat during pressurization of theballoon therein, the mold of the invention controls the outer diameterof the mounted stent, so that the profile of the mounted stent is notdisadvantageously increased during the stent mounting. The profile ofthe mounted stent can impact the ability of the stent delivery ballooncatheter to advance and cross tight lesions in the patient'svasculature.

In one aspect of the present invention, the mold may be a split-mold.The mold may have hinged halves. The mold halves swing open and close atthe hinge so that the balloon with the stent thereon can be introducedor removed from the mold without damaging the drug delivery layer of thestent. The mold therefore prevents or inhibits the damage to the drugdelivery layer which can otherwise occur with tubular radial restrainingmembers which don't open up for introduction of the balloon catheter andwhich must be cut off the balloon catheter after the stent mounting.Additionally, the mold of the invention is reusable, and provides foraccurate, uniform heating which does not vary with each subsequent use.

In another aspect of the invention, the mold body defining the entirelength of the bore and outer surface of the mold is formed of metal. Asa result, the metal mold substantially uniformly heats the entire lengthof the balloon within the bore of the mold. However, in yet anotheraspect of the invention, the mold has a body with a heat conductingmetallic section and an insulating non-metal section, so that heatingthe mold selectively heats sections of the balloon within the bore ofthe mold. The insulating section of the mold insulates the drug-deliverystent during the stent mounting procedure, so that the drug deliverystent is heated to a lower temperature than the inflatable sections ofthe balloon at either end of the stent. As a result, the balloon issufficiently heated for the stent mounting procedure without exposingthe drug-delivery stent to a disadvantageously high temperature (e.g., atemperature above the thermal limit of the drug).

A stent delivery balloon catheter of the invention generally comprisesan elongated shaft having an inflation lumen and a guidewire lumen, aballoon on a distal shaft section having an interior in fluidcommunication with the inflation lumen, and a stent releasably mountedon the balloon for delivery and deployment within a patient's bodylumen. The stent typically comprises an open-walled body of stent strutswith gaps between adjacent struts. The balloon typically has a foldednoninflated configuration with wings wrapped around the circumference ofthe balloon. In alternative embodiments, the balloon is a winglessballoon which expands by stretching from a wingless noninflatedconfiguration.

Yet another aspect of the invention is directed to a mold having astepped inner diameter comprising enlarged inner diameter sections oneither end of a middle section. During stent mounting, the stepped innerdiameter forms one or more external shoulders in the balloon. Theballoon shoulders are located adjacent the end(s) of the stent, toprevent or inhibit the stent from moving longitudinally relative theballoon during delivery and deployment of the stent. The balloonexternal shoulders have an outer diameter larger than the outer diameterof the unexpanded stent, and thus provide a barrier that the stent wouldhave to overcome in order to move longitudinally relative to theballoon. The external shoulders are thus molded into the balloonmaterial during stent mounting and are not the result of material addedto the shaft or balloon. As a result, the shoulders are formed withoutaffecting the stiffness transitions of the catheter.

Another aspect of the invention is directed to a method of mounting astent on a stent delivery balloon catheter using the mold having astepped inner diameter. The method generally comprises introducinginflation media into the interior of the balloon, and heating theballoon, to radially expand the balloon with the stent restrained fromradially expanding by a mold around an outer surface of the stent, sothat the balloon expands into the stent gaps to embed the stent in anouter surface of the balloon, to thereby mount the stent on the balloon,wherein the mold has a stepped inner diameter so that expanding theballoon forms at least one shoulder in the balloon adjacent an end ofthe stent with an outer diameter greater than an outer diameter of themounted stent in an unexpanded configuration.

In one aspect, the invention provides a method of mounting a drugdelivery stent on a catheter balloon which provides a low profilemounted stent, and which securely and consistently mounts the stent onthe balloon for delivery and deployment within a patient's body lumenwithout damaging the drug delivery layer of the stent. The metallicmold, heated primarily by conduction during stent mounting, allowstemperature control to the mold sufficient to prevent heat damage of thedrug delivery layer. The mold is heated with a method configured toavoid the nonuniformity and irreproducibility of convective heattransfer. Additionally, the mold is configured to prevent or reduceroughening or otherwise mechanically damaging the drug delivery layer,so that the drug delivery layer release rate and drug amount are notdisadvantageously effected by the stent mounting procedure of theinvention. In still another aspect of the invention, the mold has heatconducting portions and insulating portions, and heating the moldselectively heats sections of the balloon and stent within the bore ofthe mold. In yet another aspect of the invention directed to a mold witha stepped inner diameter, the mold produces one or more shoulders in theballoon which enhance stent retention on the balloon.

In yet one further aspect of the present invention, the method mayfurther including re-crimping the catheter assembly after removal fromthe split mold. Re-crimping may be done by hand, hand tool, or using acrimping tool or machine In one aspect of the invention, the re-crimpingis performed using an MSI crimper available from Machine SolutionsIncorporated, Flagstaff Ariz. In yet another aspect of the invention,the re-crimping may be performed using a stent press machine availablefrom Advanced Cardiovascular Systems, Inc., Santa Clara, Calif.

In still another aspect of the invention, during the re-crimpingprocess, the balloons may be pressurized and heated to increase theprotrusion of balloon material into the openings in the stent pattern,thereby further increasing stent retention on the balloons. In oneaspect of the invention, the balloon may be pressurized in the range of10 to 300 pounds per square inch (psi) (7 to 207 newtons per squarecentimeter). In one aspect of the invention, the balloon and the mountedstent are heated to the range of about 100 degrees to 250 degreesFahrenheit (38 to 121 degrees Celsius) during re-crimping. In yetanother aspect of the invention, the mounted stent is heated to about130 degrees Fahrenheit (54 degrees Celsius) during re-crimping. Inanother aspect of the invention, the balloon may be pressurized fromabout 10 psi (7 newtons per square centimeter) to about 70 psi (48newtons per sq. centimeter). In yet a further aspect of the invention,the balloon may be pressurized to more or less pressure.

Re-crimping may increase the retention of the stent to the balloon,particularly if the catheter assembly is to be gas sterilized withethylene oxide (EtO). In one aspect of the invention, the methodincludes a first stage of crimping the stent on the balloon catheterassembly before sterilization. The crimping before sterilization may beperformed using any presently available crimping machine or crimpingassembly. A crimping assembly may also be referred to sometimes as acrimping press. In yet a further aspect of the invention, after thefirst stage of crimping, the balloon is pressurized and heated withinthe mold to further mount the stent on the balloon. In still anotheraspect of the invention, a second crimping of the stent on the ballooncatheter assembly is performed after removal from the mold, hereinafteralso referred to as re-crimping.

In one aspect of the present invention, the method includes re-crimpingthe catheter assembly after removal from a split mold process. Duringthe split mold process, pressure is applied to the balloon, and heat isapplied to the balloon-stent assembly. It is after the split moldprocess that the balloon is likely to pull away from the stent,especially after EtO sterilization. Re-crimping is advantageous insecuring the stent onto the balloon after the split mold process andwhen sterilization is accomplished by EtO sterilization. Re-crimping mayalso be advantageous in securing the stent onto the balloon after thesplit mold process when other sterilization methods are used.

In accordance with certain aspects of the present invention there may beprovided a stent crimping assembly as disclosed in U.S. Pat. No.6,840,081 filed Nov. 18, 2002 and entitled “ASSEMBLY FOR CRIMPING ANINTRALUMINAL DEVICE OR MEASURING THE RADIAL STRENGTH OF THE INTRALUMINALDEVICE AND METHOD OF USE” which issued Jan. 11, 2005, the entirecontents of which are incorporated herein by reference.

In further accordance with the present invention, there may be provideda stent crimping assembly as disclosed in U.S. Ser. No. 10/330,016 filedDec. 26, 2002 and entitled “ASSEMBLY FOR CRIMPING AN INTRALUMINAL DEVICEAND METHOD OF USE” the entire contents of which are incorporated hereinby reference.

One aspect of the present invention is a method of mounting a stent on aballoon catheter, including positioning the stent on a balloon of theballoon catheter and applying a first radially compressive force on anouter surface of the stent, thereby decreasing the outer diameter of thestent on the balloon catheter. The method also includes pressurizing andheating the balloon while restricting radial expansion of the outersurface of the stent. Yet a further aspect of the invention includesapplying a second radially compressive force on the outer surface of thestent.

At least one aspect of the invention is a method of mounting a stent ona balloon catheter. The method includes positioning a stent on a ballooncatheter, the balloon catheter having an elongated shaft with aninflation lumen and a guidewire lumen and an inflatable balloon on adistal shaft section with an interior in fluid communication with theinflation lumen. The stent has an open-walled body of stent struts withgaps between adjacent stent struts. The method further includes applyinga first radially compressive force on an outer surface of the stent andthereby decreasing the outer diameter of the stent on the ballooncatheter. In yet another aspect, the invention includes heating theballoon and introducing inflation media into the interior of the balloonto radially expand the balloon with the stent restrained from radiallyexpanding, so that the balloon expands into the stent gaps to embed thestent in an outer surface of the balloon, and thereby mount the stent onthe balloon. In at least one aspect of the invention, the stent isrestrained from radially expanding by a mold. In yet one other aspect ofthe invention, the method includes removing the inflation media from theballoon interior and applying a second radially compressive force on anouter surface of the stent. In at least another aspect of the invention,one factor in increased retention of the stent on the balloon is thatthe second radially compressive force decreases the outer diameter ofthe stent on the balloon catheter.

Still another aspect of the invention is a method of increasingretention of an intravascular device on a balloon catheter, including afirst stage of crimping the intravascular device onto a balloon of theballoon catheter, a second stage of heating and pressurizing theballoon, and a third stage of re-crimping the intravascular device ontothe balloon of the balloon catheter.

Other features and advantages of the invention will become more apparentfrom the following detailed description of preferred embodiments of theinvention, when taken in conjunction with the accompanying exemplarydrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an isometric view of a mold useful in a method which embodiesfeatures of the invention, in which a drug delivery stent is mountedonto a balloon catheter.

FIG. 2 is an isometric view of the mold of FIG. 1 in a closedconfiguration, illustrating a distal section of a balloon catheterwithin the mold.

FIG. 3 is a longitudinal cross sectional view illustrating the mold ofFIG. 2 with heating platens on an outer surface of the mold during amethod of mounting a drug delivery stent on the balloon of the ballooncatheter.

FIG. 4 is a diagrammatic transverse cross section of the assembly ofFIG. 3, taken along line 4-4.

FIG. 5 is a perspective view of the mold of FIG. 3 in an openconfiguration allowing for removal from the mold of the stent deliveryballoon catheter having the drug delivery stent mounted on the balloon.

FIG. 6 is an elevational view of the stent delivery balloon catheter ofFIG. 5 after being removed from the mold.

FIG. 7 is a transverse cross sectional view of the stent deliveryballoon catheter of FIG. 6, taken along line 7-7.

FIG. 8 illustrates a stent delivery balloon catheter embodying featuresof the invention, in which the balloon forms shoulders adjacent the endsof the stent.

FIG. 9 illustrates a mold useful in a method of mounting a stent on aballoon catheter, having a stepped inner diameter, to form the shouldersin the balloon.

FIG. 10 illustrates a longitudinal cross sectional view of analternative embodiment of a stepped inner diameter mold useful in amethod of mounting a stent on a balloon catheter, in which end portionsof the middle section of the mold have a smaller inner diameter than theportion of middle section therebetween.

FIG. 11 is an isometric view of an alternative mold useful in a methodembodying features of the invention, having an insulating non-metal bodyportion and a metal body portion.

FIG. 12 illustrates a longitudinal cross sectional view of the moldbottom half of FIG. 11, taken along line 12-12.

FIG. 13 is an isometric view of an alternative partially insulating molduseful in a method embodying features of the invention, having ametallic body with insulating non-metal inserts.

FIG. 14 is a box-and-whisker plot of dislodgement data for stentsfollowing EtO sterilization.

FIG. 15 which is a means plot of dislodgement data for stents followingEtO sterilization.

FIG. 16 is a plot of crimped stent O.D.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

FIG. 1 illustrates a metal mold 10 useful in a method of mounting a drugdelivery stent on a balloon catheter, embodying features of theinvention. Mold 10 generally comprises a split metal body 11 with abottom half, a top half, and a polished bore 12 configured to receive aballoon catheter therein. In the embodiment illustrated in FIG. 1, thetop and bottom halves of the mold are joined by a hinge, and the mold isillustrated in an open configuration. FIG. 2 illustrates the mold in aclosed configuration with a distal section of a balloon catheter 20 inposition within the mold.

FIG. 3 illustrates the mold 10 with the distal section of the ballooncatheter 20 therein, partially in longitudinal cross section, during amethod of mounting a drug delivery stent on the balloon catheter 20. Theballoon catheter 20 has an elongated shaft 21 with a balloon 22 on adistal section thereof and a drug delivery stent 23 on the balloon. Theballoon 22, with the drug delivery stent 23 thereon, are completelycontained within the polished bore 12 of the mold 10. FIG. 4 illustratesa diagrammatic transverse cross sectional view of FIG. 3, taken alongline 4-4.

A method of releasably mounting the drug delivery stent 23 on theballoon 22 generally comprises positioning the drug delivery stent 23 onthe uninflated balloon 22 of the balloon catheter 20. The stent istypically mechanically crimped (i.e., radially collapsed) down onto theballoon 22. A distal end section of the catheter 20 is placed within themold, to position the balloon with the crimped stent 23 thereon withinthe polished bore 12 of the mold 10. In one embodiment, the mold is asplit-mold with hinged halves. The hinged halves of the mold are closedtogether, and the balloon 22 is pressurized by introducing inflationfluid into the interior of the balloon 22 and heated to an elevatedtemperature. In a presently preferred embodiment, the balloon ispressurized and then heated in the pressurized condition. In analternative embodiment, the balloon is simultaneously pressurized andheated. The balloon material at the elevated temperature and pressure isforced into the gaps in the wall of the stent 23, to embed the stentwithin the outer surface of the balloon. FIG. 3 illustrates the balloonin the pressurized and heated state, with the stent contacting thepolished inner surface of the bore of the mold to radially restrain thestent from radially expanding. In one embodiment, the balloon ispressurized to a relatively high pressure of about 15 to about 23 atm,more specifically about 19 to about 21 atm. The balloon is then cooledin the mold prior to depressurization of the balloon, and the cooledballoon depressurized, and the balloon catheter removed from the moldwith the stent mounted on the balloon. FIG. 5 illustrates the mold 10 inan open configuration facilitating removal of the balloon catheter 20therefrom after the stent 23 is mounted onto the balloon 22.

The mold bore 12 is defined by a polished inner surface of the top andbottom halves of the mold. In a presently preferred embodiment, thepolished inner surface has a polish finish of about 0.4 microns or less.The bore is polished by techniques known in the art, such as honing. Thepolished inner surface contacts the stent, and provides a smooth surfacewhich prevents or inhibits roughening the surface of the drug deliverystent 23 during the stent mounting procedure.

In the embodiment illustrated in FIGS. 1-5, the diameter of the bore 12is the same along the entire length of the mold 10. The bore 12 ispreferably formed by machining so that the diameter of the bore ishighly accurate and uniform (i.e., the diameter varies by no more than±0.025 mm along the length of the mold, and multiple molds can be madehaving the same dimensions). The bore 12 is preferably machined withinthe block which forms the body of the mold 10, with the two halves ofthe mold 10 in place together during the machining As a result, the topand bottom sections of the bore 12 perfectly and repeatably matetogether when the two halves of the mold 10 are closed together. In apresently preferred embodiment, the diameter of the mold bore 12 isslightly larger than the outer diameter of the crimped stent 23 on theballoon 22. As a result, the diameter of the mold bore 12 is largeenough to avoid scuffing/damaging the drug delivery layer of the stent23 when the balloon 22 and stent 23 crimped thereon are placed withinthe bore 12. In an alternative embodiment, the diameter of the mold bore12 is equal to the diameter of the crimped stent 23 on the balloon 22,so that the stent does not radially expand during the stent mounting.Each half of the mold 10 preferably has relatively thin walls, e.g.,with a wall thickness of not greater than about 0.25 to about 0.5 mm, atits thinnest along a midline of the bore 12 of the mold (i.e., the wallthickness from the outer surface of the mold half to the bore), toprovide fast heating and cooling within the bore 12 of the mold 10.

In accordance with the invention, the balloon 22 is heated by heatingthe mold 10 with a heat transfer medium which provides very accuratetemperature control to the mold 10. In the embodiment illustrated inFIG. 3, the heat transfer medium is a conductive heating element memberin the form of metal platens 30. The metal platens 30 have a heatingelement (not shown) such as a resistive heater which heats the metal ofthe platens, and an inner surface typically configured to correspond tothe outer surface of the mold 10. In the illustrated embodiment, theinner surface of the platens 30 and the outer surface of the mold 10 areflat, although, in alternative embodiments (not shown), the surfaceshave irregular mating surfaces designed to increase the surface areathereof. The temperature at the surface of the platens 30 is veryaccurately controllable, so that, with the surface of the metal platens30 pressed against the outer surface of the mold 10, the temperature ofthe mold can be very accurately controlled (i.e., with a tolerance whichis not larger than about ±2 degrees F., more preferably with a toleranceof about ±1 degree F.).

With the balloon catheter 20 in position within the bore 12 of the mold10, the mold 10 is slid into the space between the metal platens 30, andthe metal platens 30 brought into contact with the outer surface of thetop and bottom halves of the mold, to thereby heat the mold 10. The mold10 is heated to an elevated temperature sufficient to soften the balloon22 but lower than the thermal limit of the drug of the drug deliverystent 23. In a presently preferred embodiment, the temperature withinthe mold 10 is below a temperature which would cause the drug deliverylayer of the stent 23 to flow. However, in an alternative embodiment inwhich the drug delivery layer of stent 23 is heated and flows somewhatat the elevated temperature, the smooth inner surface of the polishedbore 12 causes the drug delivery layer to remain uniform in thicknesswithout a roughened or irregular exterior. In one embodiment, the mold10 is heated to a temperature of about 160° F. to about 190° F., withthe balloon catheter 20 therein during the stent mounting procedure, tosoften a balloon formed of polymeric material.

The metal platens 30 have a relatively high thermal conductivity, higherthan that of air at least in the temperature range of interest,providing a relatively fast rate of heating. In one embodiment, the mold10 is in contact with the heating platens 30 for not greater than about120 seconds, and more specifically for about 60 to about 120 secondsduring the stent mounting procedure. In contrast, hot air would takesignificantly longer, and for example not less than about 120 seconds(e.g., on the order of about 120 to about 240 seconds), to heat the moldto the desired temperature. The platens 30 and mold 10 are configured toprovide a fast heating rate in combination with fine control of theelevated temperature, for improved mounting of the drug delivery stent23 without damage to the drug delivery layer.

The platens 30 have a length which, in one embodiment, is at least aslong as the stent 23, and the platens are brought into contact with alength of the mold 10 corresponding to the location of the drug deliverystent 23 therein. In the embodiment illustrated in FIG. 3, the platensare longer than the stent but shorter than the balloon, although avariety of suitable configurations can be used including platens havinga length which is shorter than the stent, or platens having a lengthequal to the length of the mold 10. In a presently preferred embodiment,the platens have a length which is at least as long as, or substantiallyequal to, the length of the inflatable section of the balloon (i.e., theworking length and tapered sections). Although discussed primarily interms of the embodiment in which the mold is heated with platens 30,alternative heating mediums that heat primarily by conduction can beused including a hot liquid bath. In the embodiment using a hot liquidbath (not shown), the mold 10 has seals (not shown) at either end of themold which seal around the balloon catheter 20 to prevent the liquid orhumidity of the hot liquid bath from contacting the drug delivery stent23 within the mold 10 when the mold is submerged within the bath.

FIG. 6 illustrates the stent delivery balloon catheter 20 embodyingfeatures of the invention, after removal from the mold 10 with the drugdelivery stent 23 mounted on the balloon 22. In the illustratedembodiment, the catheter shaft 21 comprises an outer tubular member 24defining an inflation lumen 25 therein, and an inner tubular member 26defining a guidewire lumen 27 therein configured to slidingly receive aguidewire 28. Specifically, in the illustrated embodiment, the coaxialrelationship between outer tubular member 24 and inner tubular member 26defines annular inflation lumen 25. In the embodiment illustrated inFIG. 6, the guidewire lumen 27 extends to the proximal end of thecatheter. Inflatable balloon 22 has a proximal skirt section sealinglysecured to the distal end of outer tubular member 24 and a distal skirtsection sealingly secured to the distal end of inner tubular member 26,so that the balloon interior is in fluid communication with inflationlumen 25. An adapter 29 at the proximal end of catheter shaft 21 isconfigured to provide access to guidewire lumen 27, and to directinflation fluid through the arm into inflation lumen 25. As best shownin FIG. 7 illustrating a transverse cross section of the ballooncatheter of FIG. 6, taken along line 7-7, the stent gaps are partiallyfilled by the balloon material so that the balloon material contacts andpartially encapsulates the side surfaces of the stent struts, tosecurely mount the stent on the balloon. In an alternative embodiment(not shown), the balloon material completely fills the stent gaps tofully encapsulate the side surfaces of the stent struts. In theembodiment illustrated in FIGS. 6 and 7 the portions of the balloonwhich protrude between the stent struts have an outer surface flush withthe outer surface of the stent.

FIG. 6 illustrates the balloon 22, in a folded configuration with wingswrapped around the circumference of the balloon prior to completeinflation of the balloon. The balloon 22 typically has two or more, andmost preferably three wings in the noninflated configuration, whichunwrap during inflation of the balloon 22. For ease of illustration, asubstantial gap is illustrated between the inner surface of theinflatable balloon interior and the shaft inner tubular member 26 inFIGS. 6 and 7, although it should be understood that the noninflatedballoon is typically collapsed down around to inner tubular member inthe noninflated configuration. The balloon expands to a generallycylindrical inflated configuration with a central working lengthinflated section, a proximal inflated conical tapered section proximalto the stent (and distal to the proximal skirt section), and a distalinflated conical tapered section distal to the stent (and proximal tothe distal skirt section). FIG. 6 illustrates the stent 23 mounted onthe central, working length section of the balloon 22, prior to completeexpansion. The distal end of catheter 20 may be advanced to a desiredregion of the patient's body lumen in a conventional manner with theballoon in the noninflated configuration, and the balloon 22 inflated bydirecting inflation fluid into the balloon interior to expand the stent23. The balloon is then deflated, leaving the drug delivery stent 23implanted in the body lumen.

The stent 23 generally comprises an open-walled tubular body ofinterconnected, spaced-apart stent struts 31 with gaps 32 betweenadjacent stent struts. In the illustrated embodiment, the stent struts31 form rings which have a serpentine wave pattern of opposed turns andwhich are longitudinally spaced apart and connected by links 33.However, the stent 23 can have a variety of suitable configurations asare conventionally known. The tubular body of the stent 23 is typicallya biostable material such as a metal, although it can alternatively beformed of a bioabsorable material. In a presently preferred embodiment,the drug delivery layer is a coating (not shown) applied to the surfaceof the tubular body of the stent 23.

Although the embodiment illustrated in FIG. 6 is directed to embeddingthe drug delivery stent 23 in the outer surface of the layer of asingle-layered balloon, it should be understood that the balloon canalternatively be formed of multiple layers or with an outer sleevemember, so that embedding the stent into the balloon embeds the stent inthe outer surface of the outer most layer or outer sleeve of theballoon.

FIG. 8 illustrates an alternative embodiment of a stent delivery ballooncatheter 40 embodying features of the invention, having an elongatedshaft 41 and a balloon 42 on a distal shaft section with a proximalexternal shoulder 44 adjacent a proximal end of the stent 43 with anouter diameter larger than the outer diameter of the nonexpanded stentmounted on the balloon, and a distal external shoulder 45 adjacent adistal end of the stent 43 with an outer diameter larger than the outerdiameter of the nonexpanded stent mounted on the balloon. Alternatively,the balloon can have only one of the proximal 44 or distal 45 externalshoulders. For example, in one embodiment (not shown), the balloon hasthe distal external shoulder 45, and not the proximal external shoulder44. The external shoulders 44, 45 are located along the proximal anddistal inflatable sections of the balloon (e.g., along the sections ofthe balloon which inflate to form the proximal and distal conicaltapered sections in the inflated configuration, at the junction betweenthe inflatable conical tapered section of the balloon and the end of theworking length section). The stent 43 is similar to drug delivery stent23 discussed above in relation to the embodiment of FIG. 1.

In the illustrated embodiment, the balloon 42 comprises an inner layer46 and an outer sleeve member 47 which defines the outer surface of theexternal shoulders 44, 45. The outer sleeve 47 is typically formed of arelatively low melting point elastomeric polymer. In the embodimentillustrated in FIG. 8, molding the external shoulders 44, 45 in theouter sleeve 47 of the balloon also forms shoulders in the balloon innerlayer 46.

The balloon 42 is illustrated in a partially inflated configuration inFIG. 8 for ease of illustration, but it should be understood that theworking length of the balloon is typically collapsed down to the shaftinner tubular member in the noninflated configuration for advancementwithin the patient's body lumen. In one embodiment, the balloon inflatesto a cylindrical, fully inflated configuration (i.e., with no shoulders44, 45 in the outer surface of the expanded balloon). The shoulders 44,45 thus substantially disappear as the balloon expands, with the workinglength of the balloon expanding to define the maximum inflated diameterof the balloon, and the conical sections on either end of the workinglength section tapering away from the working length section to asmaller outer diameter in the inflated configuration.

In a method of mounting the stent 43 on the balloon catheter 40 to formthe stent delivery system of FIG. 8, the radial restraining mold 50 hasa stepped inner diameter which forms the external shoulders 44, 45 inthe balloon during the stent gripping. FIG. 9 illustrates ballooncatheter 40 within a radial restraining mold 50 having an inner chamber51 configured for receiving the balloon portion of the balloon catheter40. The radial restraining mold 50, similar to the embodiment of FIG. 1,typically has a bottom half attached by hinges to a top half, whichfacilitates positioning the balloon portion of the catheter in the innerchamber 51 of the mold. The inner chamber 51 has enlarged inner diametersections 52 and 53 on either end of a middle section 54. The balloon isillustrated with the outer sleeve 47 and stent 43 thereon, duringpressurization of the balloon to mount the stent on the balloon. As setforth above, the mold 50 radially restrains the stent 43 as inflationmedia is introduced into the interior of the balloon and the mold isheated to heat the balloon, so that the balloon expands into the stentgaps and the external shoulders 44, 45 are formed in the balloon by theenlarged inner diameter sections 52, 53 of the mold 50. In theembodiment illustrated in FIG. 8, the inner surface of the balloon alsohas a stepped configuration at the shoulders. As a result, a gap existsbetween the inner surface of the balloon at the shoulders 44, 45 and theouter surface of the shaft (or the outer surface of a radiopaque marker(not shown) on the shaft if the radiopaque marker is located beyond theend of the stent) in the noninflated configuration. Although theembodiment illustrated in FIGS. 8 and 9 has the outer sleeve 47 on theballoon inner layer 46, it should be understood that in an alternativeembodiment (not shown) the outer sleeve 47 is omitted. The method fullyor partially embeds the stent 43 in the balloon 42 depending on theballoon material and stent mounting method conditions.

FIG. 10 illustrates a longitudinal cross sectional view of analternative radial restraining mold 60 with a stepped inner diameter, inwhich end portions 65, 66 of the middle section 64 of the mold have asmaller inner diameter than the portion of middle section 64therebetween. The reduced inner diameter end portions 65, 66, cause theends of the stent 30 to further embed down into the balloon during thestent mounting. Embedding the ends of the stent to a greater degree thana central section of the stent improves stent retention andadvanceability of the system.

In a presently preferred embodiment, the mold 10/50/60 is formed ofmetal, so that the metallic body of the mold defines the entire lengthof the bore that receives the balloon, and defines an outer surface ofthe mold. The metallic body substantially uniformly heats the entirelength of the balloon within the mold. In an alternative embodiment, themold selectively heats sections of the balloon within the bore of themold (i.e., the mold has sections which differentially conduct heat).For example, FIG. 11 illustrates an isometric view of an alternativeradial restraining mold 70, having a body 71 formed of an insulatingmaterial such as a plastic with metal portions 72, which allows forselective heating of the balloon portion of a catheter. The metalportions 72 are heat conducting, and the insulating (e.g., plastic) body71 is not heat conducting, or at least is substantially less heatconducting than the metal portions. For example, when a metal portionwas heated to 163° F. (73° C.), the maximum temperature measured in theadjacent insulating plastic portion was 109° F. (43° C.). As a result,the balloon portion proximal and distal to the stent can be placed atthe metal portions 72, with the balloon central working length section(having the stent thereon) located between the metal portions 72, sothat the plastic of the mold body insulates the working length sectionof the balloon portion from the elevated temperatures used during thestent mounting.

Insulating at least the central working length section of the balloonportion from heat protects the drug delivery coating of the stent fromdamage during the stent mounting procedure. Depending on the length ofthe metal portions 72, the plastic body 71 typically also insulates theballoon skirt sections (secured to the shaft) from heat of the heattransfer medium during the stent mounting procedure.

In a presently preferred embodiment, the insulating material forming themold body 71 is a plastic such as polyetheretherketone (PEEK), or amachinable polyimide such as Vespel, although non-plastic insulatingmaterials can alternatively be used such as ceramics including Macor (amachinable glass ceramic).

FIG. 12 illustrates a longitudinal cross sectional view of the bottomhalf of the mold 70 of FIG. 11, taken along line 12-12. In a presentlypreferred embodiment, the metal portions 72 have, along at least asection thereof, a larger wall thickness (from the inner to the outersurface) than the adjacent sections of the plastic body 71 so that themetal portions 72 have at least a section which protrudes from the outersurface of the plastic body 71. The heating platens (discussed above inrelation to the embodiment of FIG. 3) will therefore contact theprotruding outer surface of the metal portions 72 without contacting theplastic body 71 during the stent mounting procedure. The air gap betweenthe heating platens and the plastic body 71 sections will further reduceheat transfer to the drug delivery layer of a stent within the mold 70.In the illustrated embodiment, the plastic body 71, which together withthe metal portions 72 defines the length of the bore receiving theballoon, is within an outer housing, typically formed of a metal, whichsurrounds the outer surfaces of the plastic body. The illustrated metalportions 72 have a section with a sufficiently large wall thickness suchthat the metal portions 72 protrude from the outer surface of the outerhousing.

FIG. 13 illustrates an isometric view of an alternative embodiment of aselective heating mold 80 which embodies features of the invention,having a metallic body 81 with insulating plastic inserts 82. In theillustrated embodiment, three plastic inserts 82 are present, positionedat sections of the mold configured to receive the central working lengthsection of balloon, and the skirt sections of the balloon secured to theshaft. The sections of the metallic body 81 of the mold located betweenthe adjacent plastic inserts 82 are configured to receive the inflatableconical sections of the balloon (i.e., the balloon sections which extendbetween the central working length and the skirt sections of theballoon). The plastic inserts 82 preferably have a wall thickness whichis less than the wall thickness of the metallic body 81. As a result,the metallic body 81 preferably defines the outer surface of the moldalong the entire length thereof, and the metallic body 81 together withthe plastic inserts 82 define sections of the bore of the mold.Alternatively, the wall thickness of the plastic inserts is equal to thewall thickness of the metallic body, so that the metallic body togetherwith the plastic inserts define sections of the outer surface of themold 80.

The dimensions of the stent delivery balloon catheter 20, 40 aredetermined largely by the size of the balloon and guidewire to beemployed, the catheter type, and the size of the artery or other bodylumen through which the catheter must pass or the size of the stentbeing delivered. Typically, the outer tubular member 24 has an outerdiameter of about 0.025 to about 0.04 inch (0.064 to 0.10 cm), usuallyabout 0.037 inch (0.094 cm), and the wall thickness of the outer tubularmember 24 can vary from about 0.002 to about 0.008 inch (0.0051 to 0.02cm), typically about 0.003 to 0.005 inch (0.0076 to 0.013 cm). The innertubular member 26 typically has an inner diameter of about 0.01 to about0.018 inch (0.025 to 0.046 cm), usually about 0.0+16 inch (0.04 cm), anda wall thickness of about 0.004 to about 0.008 inch (0.01 to 0.02 cm).The overall length of the catheter 20, 40 may range from about 100 toabout 150 cm, and is typically about 143 cm. Preferably, balloon 22, 42has a length of about 0.8 cm to about 6 cm, and an inflated workingdiameter of about 2 mm to about 10 mm.

Inner tubular member 26 and outer tubular member 24 can be formed byconventional techniques, for example by extruding and necking materialsalready found useful in intravascular catheters such a polyethylene,polyvinyl chloride, polyesters, polyamides, polyimides, polyurethanes,and composite materials. The various components may be joined usingconventional bonding methods such as by fusion bonding or use ofadhesives. Although the shaft is illustrated as having an inner andouter tubular member, a variety of suitable shaft configurations may beused including a dual lumen extruded shaft having a side-by-side lumensextruded therein. Similarly, although the embodiment illustrated in FIG.6 is an over-the-wire type balloon catheter, the catheter of thisinvention may comprise a variety of intravascular catheters, such asrapid exchange type balloon catheters. Rapid exchange cathetersgenerally comprise a shaft having a relatively short guidewire lumenextending from a guidewire distal port at the catheter distal end to aguidewire proximal port spaced a relatively short distance from thedistal end of the catheter and a relatively large distance from theproximal end of the catheter.

The terms crimping and compressing as used herein are meant to beinterchangeable and mean that the diameter of the stent is reduced tosome degree. Typically, balloon-expandable stents 23 are known bypersons having ordinary skill in the art to be “crimped” onto theballoon 22 portion of a catheter 20 while self-expanding stents arecompressed onto a mandrel or sheath and then inserted into a catheter.The term re-crimping as used herein refers to a second radiallycompressive force on an outer surface of the stent following a firstradially compressive force on an outer surface of the stent. There-crimping may use the same crimping apparatus and/or method as thefirst crimping, or a different crimping apparatus and/or method. Bothcrimping and re-crimping include applying a radially compressive forceon an outer surface of the stent and thereby decreasing the outerdiameter of the stent on the balloon catheter. Re-crimping as usedherein also refers to applying a radially compressive force on an outersurface of the stent after removal from the mold 10. The termpre-mounting as used herein refers to the stent being placed onto thecatheter assembly and compressed before the stent mounted catheter isinserted into the crimping assembly for the first crimping process. Inone embodiment, pre-mounting the stent onto the balloon of the catheterassembly includes compressing the stent onto the catheter with fingerpressure before the stent mounted catheter is inserted into the crimpingassembly.

Further, while reference is made herein to crimping or compressing“stents,” the invention can be used with any intraluminal device toreduce the diameter or measure radial strength. Thus, the invention isparticularly useful with stents, grafts, tubular prostheses, embolicdevices, embolic filters, and embolic retrieval devices.

The crimping processes referred to herein may be performed using thecrimping assembly or apparatus referred to above or any other acceptablestent crimping assembly, apparatus, or method known in the art. Acrimping assembly or apparatus may also be referred to sometimes as acrimping press. In one embodiment of the invention, a stent crimpingassembly is used to crimp an expandable stent 23 onto the balloon 22portion of a balloon catheter 20, however, the invention can be usedwith self-expanding stents as well. Examples of stent assemblies thatmay be used to crimp an expandable stent onto a balloon catheter includea stent crimping assembly as disclosed in U.S. Pat. No. 6,840,081 filedNov. 18, 2002 and entitled “ASSEMBLY FOR CRIMPING AN INTRALUMINAL DEVICEOR MEASURING THE RADIAL STRENGTH OF THE INTRALUMINAL DEVICE AND METHODOF USE” which issued Jan. 11, 2005, the entire contents of which areincorporated herein by reference and/or a stent crimping assembly asdisclosed in U.S. Ser. No. 10/330,016 filed Dec. 26, 2002 and entitled“ASSEMBLY FOR CRIMPING AN INTRALUMINAL DEVICE AND METHOD OF USE” theentire contents of which are incorporated herein by reference.

In at least one embodiment, the invention includes a method of mountinga stent 23 on a balloon catheter 20. The stent is positioned on theballoon catheter by hand or apparatus. In at least one embodiment, thestent is pre-mounted onto the balloon 22 of the balloon catheter by aslight compressive pressure, for example, hand pressure. Afterpositioning of the stent on the balloon, a first radially compressiveforce is applied on an outer surface of the stent, thereby decreasingthe outer diameter of the stent on the balloon catheter. After applyingof the first radially compressive force, the balloon is pressurized andheated while restricting radial expansion of the outer surface of thestent. In one embodiment, the pressurizing and heating of the balloon isdone in a mold, for example, a split mold, configured to restrict theradial expansion of the outer surface of the stent. During thepressurizing and heating, outpouchings of the balloon may extend betweenundulations of the stent, further securing the stent on the balloon.However, the balloon may pull away from the stent somewhat as theballoon cools. The pulling away of the balloon from the stent may beexaggerated during EtO sterilization. Therefore, at least one embodimentincludes applying a second radially compressive force on the outersurface of the stent. The second radially compressive force may decreasethe outer diameter of the stent on the balloon catheter, wherein thestent is more securely mounted on the balloon. The first and/or secondradially compressive forces may be applied by hand, by hand tool, or bymachine, for example, a crimping maching. In at least one furtherembodiment, the assembly including the stent and balloon catheter maythen be sterilized, for example, by EtO sterilization.

In at least one embodiment, the invention includes a method ofincreasing stent 23 retention on a balloon catheter 20. In oneembodiment, the method includes a first stage of crimping the stent ontothe balloon catheter before placing the balloon catheter with the stentmounted thereon in the mold 10, and a second stage of crimping of thestent onto the balloon catheter after the split mold process, describedelsewhere herein, and before sterilization of the stent and ballooncatheter assembly.

In a further embodiment, the invention is a method of increasingretention of an intravascular device on a balloon catheter, including afirst stage of crimping the intravascular device onto a balloon of theballoon catheter, a second stage of heating and pressurizing theballoon, and a third stage of re-crimping the intravascular device ontothe balloon of the balloon catheter.

In another embodiment, after the first stage of crimping, the stent 23crimped on the balloon 22 is submitted to the split mold processdescribed in greater detail above. After the first stage of crimping andthe split mold process, the undulating rings of the stent indent intothe balloon 22 resulting in out pouching or pillowing of the ballooninto the openings between the undulations of the stent. In yet anotherembodiment, heating of the balloon and introducing inflation media intothe interior of the balloon radially expands the balloon. The stent isrestrained from radially expanding, for example, by the mold around anouter surface of the stent. As the balloon radially expands under heat,the balloon expands into the stent gaps to embed the stent in an outersurface of the balloon, thereby mounting the stent on the balloon.

However, a loss of stent retention may occur if sterilization of theballoon catheter 20 with the stent mounted thereon is performed directlyafter the split mold process. The loss of stent retention typicallyoccurs with EtO (ethylene oxide) sterilization. One factor in the lossof stent retention may be that the balloon shrinks and pulls away fromthe stent during the sterilization process. Yet another factor in theloss of stent retention may be that the balloon shrinks and pulls awayfrom the stent as it cools after the split mold process.

In one embodiment of the invention, the method may include applying atleast one radially compressive force on the outer surface of the stent23 that has been mounted on the balloon catheter 20 after removal fromthe mold 10. The mold may be a split mold. In one embodiment, the stentis pre-mounted on the balloon and positioned in the mold. After removalfrom the mold, a radially compressive force is applied on the outersurface of the stent before sterilization of the stent-balloon catheterassembly.

During the split mold process, pressure is applied to the balloon 22,and heat is applied to the balloon-stent assembly. It is after the splitmold process that the balloon may pull away from the stent 23.Re-crimping is advantageous in securing the stent onto the balloon afterremoval from the mold 10. The advantage of re-crimping the stent ontothe balloon catheter 20 is that the re-crimping may increase theretention of the stent to the balloon, particularly if the catheterassembly is to be gas sterilized with ethylene oxide (EtO). In at leastone embodiment, the re-crimping is performed after the split moldprocess without another stage of crimping having been performed beforethe split mold process.

Re-crimping may be done by hand, using a crimping tool, a crimpingmachine, a crimping press, and/or a crimping assembly. In one preferredembodiment, the re-crimping is performed using an MSI crimper availablefrom Machine Solutions Incorporated, Flagstaff Ariz. In one embodiment,the re-crimping may be performed using a stent press machine availablefrom Advanced Cardiovascular Systems, Inc., Santa Clara, Calif.

In one embodiment, during the crimping and/or re-crimping process theballoon 22 may be pressurized and heated to increase the protrusion ofballoon material into the openings in the stent 23 pattern, therebyfurther increasing stent retention on the balloon. In yet anotherembodiment of the invention, the balloon may be pressurized in the rangeof 10 to 300 pounds per square inch (psi) (7 to 207 newtons per squarecentimeter).

In at least one embodiment of the invention, the balloon 22 having thestent 23 mounted thereon is heated to the range of about 70 degrees to250 degrees Fahrenheit (21 to 121 degrees Celsius) during re-crimping.In one embodiment the mounted stent is heated to about 130 degreesFahrenheit (54 degrees Celsius) during re-crimping. In one embodiment,the balloon may be pressurized to about 70 psi (48 newtons per sq.centimeter). In other embodiments, the balloon may be pressurized tomore or less pressure. In one embodiment, processing time during there-crimping is in the range of one second to five minutes. In at leastone embodiment, the processing time is approximately 10 seconds.

The split mold process described above may include applying heat andpressure to the balloon 22 and stent 23 mounted thereon, whilerestraining radially expansion of the stent, for a first period of timein order to deform the balloon so that it conforms to the contours ofthe stent. In one embodiment, the first period of time is a short periodof time, for example, 1-2 minutes. Following the split mold process, thestent delivery system is EtO sterilized. During EtO sterilization, thestent delivery system loses approximately 25% of the stent retentionforce. From examination of photos and stent OD measurements, it appearsthat the balloon is relaxing and does not conform as strongly to thecontours of the stent. This balloon relaxation is likely caused bystrain recovery due to residual stresses in the balloon material as itis exposed to temperatures above the glass transition temperature of theballoon material during the EtO process (a heat and humidity cycle).

In at least one other embodiment, the balloon 22 and stent 23 mountedthereon are exposed to heat and pressure, while restraining radiallyexpansion of the stent, for a second period of time. The intent of theprocess is to relax the polymer chains of the balloon in the “gripped”orientation, such that it reduces the tendency of the balloon to relaxduring sterilization. The higher the temperature, the less time that itwill take for the balloon polymer to set in the desired orientation.This process could be used to provide dimensional stability to anypolymer component that experiences strain recovery when exposed todownstream processing temperatures above the glass transitiontemperature of the polymer. In one embodiment, the balloon ispressurized to between about 1 pound per square inch (0.7 newtons persquare centimeter) to about 500 pound per square inch (345 newtons persquare centimeter) during at least one of the first time period or thesecond time period. In at least one embodiment, the balloon ispressurized to between about 5 (3.5 newtons per square centimeter) poundper square inch and 300 pound per square inch (207 newtons per squarecentimeter) during at least one of the first time period or the secondtime period. In at least one further embodiment, the balloon ispressurized to between about 300 pound per square inch (207 newtons persquare centimeter) pound per square inch and about 900 pound per squareinch (621 newtons per square centimeter) during at least one of thefirst time period or the second time period. This method is also usefulfor increasing retention of drug delivery stents.

In at least one embodiment, the balloon 22 and stent 23 mounted thereonmay be constrained or restrained in a mold 10, for example the radialrestraining mold 50, during the second period of time. In oneembodiment, the mold is a split-mold. The split mold may have hingedhalves. In another embodiment, the balloon 22 and stent 23 mountedthereon may be constrained or restrained in a sheath. In at least oneembodiment, the sheath used to restrain expansion of the stent is aprotective sheath, such as those known in the art, wherein the sheath isconfigured for protecting a stent mounted on a balloon during shipment.In one embodiment, the stent is restrained to a diameter close to thedesired final stent outer diameter. In one embodiment, the final stentouter diameter is the desired outer diameter of the stent just prior todelivery of the stent into the vessel to be treated.

In one embodiment, the heating process during the first time period orthe second time period could use heat provided from forced airconvection. In another embodiment, the heating process during the firsttime period or the second time period could use heat provided byconduction through the mold 10, 50. In yet another embodiment, theheating process during the first time period or the second time periodcould use the heat provided from an oven.

In one embodiment, the heating process exposes the balloon 22 and/orstent 23 to temperatures equal to, slightly below, or slightly above theglass transition temperature (Tg) of the balloon. Humidity or atransient plasticizing agent such as alcohol, acetone or other solventsuitable to the particular balloon material may also be applied to theballoon to lower the Tg.

In one embodiment, the second time period has a duration of about 15seconds to about 48 hours. In another embodiment, the second time periodhas a duration of about 5 minutes to about 48 hours. These time periodsare by way of example, and longer or shorter time periods may be usedfor the second time period.

In one further embodiment, the balloon 22 and stent 23 mounted thereonmay be cooled during a third time period. In at least one embodiment,the cooling process during the third time period may be controlled. Therate of cooling and the amount of cooling may be controlled. In yetanother embodiment, the balloon should remain pressurized during thecooling process of the third time period. In one embodiment, the thirdtime period of cooling follows the second time period of heat andpressure. In another embodiment, the third time period of cooling isperformed following after the first time period of heat and pressure andis performed again after the second time period of heat and pressure.

In yet one further embodiment, the method of crimping the stent onto theballoon of the balloon catheter may include crimping the stent onto theballoon more than once. In one embodiment, the stent is crimped beforethe first time period of heat and pressure. In another embodiment, thestent is re-crimped at least once after the first period of heat andpressure. In still another embodiment, the stent is re-crimped after thesecond period of heat and pressure.

EXAMPLE

Referring now to FIGS. 14-16, balloon catheters 20 were divided into 3groups. Sheaths configured for restraining radial expansion of theballoons and/or stents were placed over each of the balloons 22 with thestents 23 mounted thereon. In the first group, the balloons werepressurized to 30 psi (21 newtons per square centimeter). In the secondgroup, the balloons were pressurized to 60 psi (41 newtons per squarecentimeter). The third group was a control group. The balloons of thecatheters of the first and second groups were pressurized using standardairbox and stopcock. The pressurized balloon catheters with the stentsmounted thereon were then placed in constant temperature oven set at145° F. (63 degrees Celsius) for a duration of approximately 24 hours.This extended time was chosen to increase signal.

The balloon catheters 20 were then de-pressurized and packaged pernormal operating procedures. The three test groups were then sent to EtOsterilization. All units were collected after EtO sterilization andsubmitted to the lab for randomized dislodgement testing.

The dislodgement results are shown in FIGS. 14-16. Referring now to FIG.14 which is a box-and-whisker plot of the data, this plot shows that thespread of the data is not different between the three groups but doesshow that the first group has higher values and therefore betterretention than the second and the third group. Referring now to FIG. 15which is a means plot of the data, this plot shows that the dislodgementvalues for the first group are significantly higher at the 95%confidence level. However the second group was not significantly higherthan the control and actually had a lower overall average retention.

Crimped stent data was also gathered as part of the test. The means plotfor the average crimped stent OD (outer diameter) is shown in FIG. 16.This plot shows that the averaged crimped stent OD increases withincreasing pressure with the first group averaging approximately 0.0006inch larger than the control and the second group averagingapproximately 0.0015 inch larger than the control with the differencesbetween the groups being statistically significant at the 95% confidencelevel. The crimped stent OD (outer diameter) data was smaller than theID (inner diameter) of the finished goods sheath. The deploymentpressure for one kind of stent is around 60-75 psi (41-52 newtons persquare centimeter).

The data shows that applying pressurized heat set to a stent 23 mountedon a balloon 22 does mitigate the loss of stent dislodgement forceduring EtO sterilization as long as the crimped stent OD is notsignificantly impacted. Pressurizing the system to a pressure where thestent actually begins to deploy results in no benefit to dislodgementfrom the pressurized heat set.

While the present invention is described herein in terms of certainpreferred embodiments, those skilled in the art will recognize thatvarious modifications and improvements may be made to the inventionwithout departing from the scope thereof. For example, while discussedprimarily in terms of a stent or a drug delivery stent, aspects of theinvention may be useful with an alternative prosthesis or stent (e.g., abare metal stent). Moreover, although individual features of oneembodiment of the invention may be discussed herein or shown in thedrawings of the one embodiment and not in other embodiments, it shouldbe apparent that individual features of one embodiment may be combinedwith one or more features of another embodiment or features from aplurality of embodiments.

What is claimed:
 1. A method of mounting a stent on a balloon catheter,comprising: positioning a stent on a balloon of a balloon catheter tocreate an assembly, wherein the stent includes an open-walled bodyformed from struts with gaps therebetween; placing a sheath over thestent and the balloon to restrain radial expansion of the stent and theballoon; pressurizing the balloon up to 30 psi (21 Newtons per squarecm); heating the stent and balloon assembly in a constant temperatureoven for a period of time; and depressurizing the balloon, and;providing a dislodgment value to the stent of no less than 1.3 lbf (5.8Newtons) at a 95% confidence level.
 2. The method of claim 1, wherein anoutside diameter of the stent before mounting on the balloon is no morethan 0.037 inch (0.094 cm) and the outside diameter of the stent afterthe balloon is depressurized is no more than 0.0426 inch (1.0820 cm). 3.The method of claim 1, wherein the constant temperature is 145° F. (63°C.).
 4. The method of claim 1, wherein the time period forpressurization and heating is approximately twenty-four hours.
 5. Themethod of claim 1, wherein the balloon and stent are sterilized in Etoand after the sterilization step, the dislodgement force is notsignificantly changed.
 6. The method of claim 1, wherein a drug coatingis applied to the stent prior to mounting on the balloon.
 7. The methodof claim 6, wherein the stent is crimped onto the balloon before theballoon is pressurized and before heat is applied.